Retinoic acid -- or RA -- belongs to a class of chemically related compounds called retinoids. Retinoids are naturally occurring and synthetic forms of vitamin A -- or retinol. Vitamin A-like compounds play an important role in many aspects of human health, including vision, bone growth, reproduction and immunity. Retinoid acid is also a key regulator of cellular differentiation -- the process by which cells acquire specialized functions -- which is often deregulated in cancer. The capacity of RA to regulate differentiation forms the basis for its potential and use in cancer prevention studies.
Retinoic Acid Basics
There are two categories of vitamin A; preformed vitamin A and pro-vitamin A. Preformed vitamin A, found in animal-derived foods, is converted to RA within the body. Pro-vitamin A carotenoids, found in colorful fruits and vegetables, are converted into retinol in the body. More than 500 carotenoids have been discovered, although not all can be converted to retinol in the human body. Dietary sources of retinoids and carotenoids include cod liver oil, eggs, fortified foods, such as cereals and milk, and yellow and orange fruits and vegetables, such as carrots and sweet potatoes. According to estimates by MayoClinic.com, consumption of 5 servings of fruits and vegetables can provide 50 to 60 percent of the adult recommended daily allowance for vitamin A.
Mode of Action
Retinoids such as RA travel through blood in a protein-bound form. They diffuse into cells and bind to proteins called retinoic acid receptors -- RAR. The RA-RAR complex interacts with other proteins within the cells to ultimately change the state of genes, or stretches of DNA which code for protein. More than 500 genes are through to be regulated by RA and other retinoids. One important effect of retinoids and RA on cells is to drive and maintain the differentiation of epithelial cells -- cells lining the internal surface of many organs, including eyes, respiratory, intestinal and urinary tracts.
Cancer Specific Effects
Studies on experimental animal models and cultured cancer cells have helped unravel how RA might help prevent or treat cancers. Reviews of such studies, published in "The Oncologist" and "Carcinogenesis" in 2000, indicate that retinoids can suppress the growth and even induce the death of cancer cells. Retinoids are already in use for treatment in premalignant lesions -- cellular overgrowth that is not yet cancerous, but may become cancerous. These pre-cancerous lesions include oral leukoplakia, cervical dysplasia and Xeroderma pigmentosum. A form of RA called ATRA -- all-trans retinoic acid -- is used treatment of acute promyelocytic leukemia, a type of blood cancer. Retinoids, in combination with other drugs, are also used in kidney, skin and cervical cancer treatments.
Cancer Prevention Studies
The use of retinoids in treating some precancerous lesions and cancers has established a premise for their use in cancer prevention. The toxicity associated with high vitamin A/retinoid-doses limits their use in preventing cancer in high-risk groups. Scientists are attempting to overcome this hurdle by developing synthetic retinoids with more desirable biological properties. Fenretinide, one such synthetic retinoid, is being evaluated in clinical trials for prevention of first or recurrent breast, ovarian, kidney and nervous tissue cancers. The results of clinical trials of fenretinide and other retinoids, such as ATRA and bexarotene, can help us apply retinoids for cancer prevention. Consult your doctor for clarifications on retinoic acid specific to your health concerns.
References
- Office of Dietary Supplements; National Institutes of Health; Vitamin A Fact Sheet
- "The Oncologist"; Konstantin H. Dragnev, et al.; July 2000
- "Carcinogenesis"; Laura A. Hansen, et al.; July 2000
- National Institutes of Health Clinical Trials Registry; Fenretinide+Cancer
- "Biomedical Papers of the Medical Faculty of the University Palacky"; Julius Brtko; December 2007
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